Pharmaceutical composition for immune activity or for preventing or treating cancer

Abstract

A composition according to an embodiment of the present disclosure includes a blunt-ended hairpin RNA; and porous silica particles carrying the RNA in pores thereof, wherein the porous silica particles have an average pore diameter of 7 to 25 nm, and the inside of the pores is positively charged, thus to sufficiently support the RNA and stably deliver the supported RNA into the body. The composition may improve immune activity and prevent or treat cancer.

What is claimed is: 
     
         1 . A composition, comprising:
 a blunt-ended hairpin RNA represented by Formula 1; and   porous silica particles having pores and carrying the blunt-ended hairpin RNA in the pores, the porous silica particles having an average pore diameter of 7 to 25 nm, an inside of the pores being positively charged:   
       
         
           
                 
                 
                 
               
                     
                     
                   [Formula 1] 
                 
                     
                     
                   5′-P a -((N1-X1) b -N2)-UUCG-(N3-(X2-N4) b )-3′ 
                 
                     
                     
                 
                     
                     
                   (5′-Pa-(SEQ ID NO: 28)-3′)  
                 
             
                
                
                
                
               
            
           
         
         wherein P is a phosphoric acid group 
         a is an integer of 2 to 5, and b is an integer of 1 to 5; 
         UUCG is a base to form a loop of the hairpin; 
         N1 and N2 are 2 to 4 bases selected from G or C, X1 and X2 are 1 to 5 bases selected from A or U, and the plurality of selected bases are the same as or different from one other; 
         N3 is complementarily bound with N2, X2 is complementarily bound with X1, and N4 is complementarily bound with N1; and 
         each base repeating b times is the same as or different from one another. 
       
     
     
         2 . The composition according to  claim 1 , wherein the blunt-ended hairpin RNA is represented by Formula 2: 
       
         
           
                 
                 
                 
               
                     
                     
                   [Formula 2] 
                 
                     
                     
                   5′-P a -((N1-X1) b -N2)-UUCG-(N3-(X2-N4) b )-3′ 
                 
                     
                     
                 
                     
                     
                   (5′-Pa-(SEQ ID NO: 29)-3′)  
                 
             
                
                
                
                
               
            
           
         
         wherein P is a phosphoric acid group; 
         a and b are each an integer of 2 to 4; 
         N1 and N2 are 2 to 4 bases selected from G or C, X1 and X2 are 2 to 4 bases selected from A or U, and the plurality of selected bases are the same as or different from one other; 
         N3 is complementarily bound with N2, X2 is complementarily bound with X1, and N4 is complementarily bound with N1; and 
         each base repeating b times is the same as or different from one another. 
       
     
     
         3 . The composition according to  claim 1 , wherein the blunt-ended hairpin RNA has a length of 14 to 100 nt. 
     
     
         4 . The composition according to  claim 1 , wherein the SEQ ID NO: 28 is selected from the group consisting of SEQ ID NOs: 1 to 25, and a of Formula 1 is 2 to 4. 
     
     
         5 . The composition according to  claim 1 , wherein a zeta potential of the porous silica particles carrying the blunt-ended hairpin RNA in the pores thereof is 5 to 65 mV. 
     
     
         6 . The composition according to  claim 1 , wherein the zeta potential of the porous silica particles carrying the blunt-ended hairpin RNA in the pores thereof is 35 mV or less. 
     
     
         7 . The composition according to  claim 1 , wherein the zeta potential of the particle without carrying RNA is 10 to 70 mV. 
     
     
         8 . The composition according to  claim 1 , wherein a weight ratio of the particles and the blunt-ended hairpin RNA is 1:5 to 20. 
     
     
         9 . The composition according to  claim 1 , wherein the pores extend from a surface to an inside of the particle. 
     
     
         10 . The composition according to  claim 1 , wherein a BET (Brunauer-Emmett-Teller) surface area of the particles is 280 to 680 m 2 /g, and a particle diameter is 50 to 500 nm. 
     
     
         11 . The composition according to  claim 1 , wherein the porous silica particles have the pores having an average diameter of 7 to 25 nm prepared by expanding pores of an average pore diameter of less than 5 nm of the porous silica particles. 
     
     
         12 . A method for enhancing an immune activity of a subject, the method comprising the composition of  claim 1  to the subject in need thereof. 
     
     
         13 . A method for preventing or treating cancer, the method comprising:
 administering to a subject in need thereof a composition comprising:   a blunt-ended hairpin RNA represented by Formula 1; and   porous silica particles having pores and carrying the blunt-ended hairpin RNA in the pores, the porous silica particles having an average pore diameter of 7 to 25 nm, an inside of the pores being positively charged,   
       
         
           
                 
                 
                 
               
                     
                     
                   [Formula 1] 
                 
                     
                     
                   5′-P a -((N1-X1) b -N2)-UUCG-(N3-(X2-N4) b )-3′ 
                 
                     
                     
                 
                     
                     
                   (5′-Pa-(SEQ ID NO: 28)-3′)  
                 
             
                
                
                
                
               
            
           
         
         wherein P is a phosphoric acid group; 
         a is an integer of 2 to 5, and b is an integer of 1 to 5; 
         UUCG is a base to form a loop of the hairpin; 
         N1 and N2 are 2 to 4 bases selected from G or C, X1 and X2 are 1 to 5 bases selected from A or U, and the plurality of selected bases are the same as or different from one other; 
         N3 is complementarily bound with N2, X2 is complementarily bound with X1, and N4 is complementarily bound with N1; and 
         each base repeating b times is the same as or different from one another. 
       
     
     
         14 . The method of  claim 13 , wherein the blunt-ended hairpin RNA is represented by Formula 2: 
       
         
           
                 
                 
                 
               
                     
                     
                   [Formula 2] 
                 
                     
                     
                   5′-P a -((N1-X1) b -N2)-UUCG-(N3-(X2-N4) b )-3′ 
                 
                     
                     
                 
                     
                     
                   (5′-Pa-(SEQ ID NO: 29)-3′)  
                 
             
                
                
                
                
               
            
           
         
         wherein P is a phosphoric acid group; 
         a and b are each an integer of 2 to 4; 
         N1 and N2 are 2 to 4 bases selected from G or C, X1 and X2 are 2 to 4 bases selected from A or U, and the plurality of selected bases are the same as or different from one other; 
         N3 is complementarily bound with N2, X2 is complementarily bound with X1, and N4 is complementarily bound with N1; and 
         each base repeating b times is the same as or different from one another. 
       
     
     
         15 . The method of  claim 13 , wherein the blunt-ended hairpin RNA has a length of 15 to 100 nt. 
     
     
         16 . The method of  claim 13 , wherein the SEQ ID NO. 28 is selected from the group consisting of SEQ ID NOs: 1 to 25, and a of Formula 1 is 2 to 4. 
     
     
         17 . The method of  claim 13 , wherein a zeta potential of the porous silica particles carrying the blunt-ended hairpin RNA in the pores thereof is 5 to 65 mV. 
     
     
         18 . The method of  claim 13 , wherein the zeta potential of the porous silica particles carrying the blunt-ended hairpin RNA in the pores thereof is 35 mV or less. 
     
     
         19 . The method of  claim 13 , wherein the zeta potential of the particle without carrying RNA is 10 to 70 mV. 
     
     
         20 . The method of  claim 13 , wherein a weight ratio of the particles and the blunt-ended hairpin RNA is 1:5 to 20. 
     
     
         21 . The method of  claim 13 , wherein the pores extend from a surface to an inside of the particle. 
     
     
         22 . The method of  claim 13 , wherein a BET (Brunauer-Emmett-Teller)surface area of the particle is 280 to 680 m 2 /g, and a particle diameter is 50 to 500 nm. 
     
     
         23 . The method of  claim 13 , wherein the porous silica particles have the pores having an average diameter of 7 to 25 nm prepared by expanding pores of an average pore diameter of less than 5 nm of the porous silica particles. 
     
     
         24 . The method of  claim 13 , wherein the cancer is selected from the group consisting of breast cancer, ovarian cancer, cervical cancer, prostate cancer, testicular cancer, penile cancer, genitourinary tract cancer, testicular tumor, esophageal cancer, laryngeal cancer, gastric cancer, gastrointestinal cancer, skin cancer, keratinocyte cell tumor, follicular carcinoma, melanoma, lung cancer, small cell lung carcinoma, non-small cell lung carcinoma (NSCLC), lung adenocarcinoma, squamous cell carcinoma of the lung, colon cancer, pancreatic cancer, thyroid cancer, papillary cancer, bladder cancer, liver cancer, bile duct cancer, kidney cancer, bone cancer, bone marrow disorder, lymphatic disorder, hair cell cancer, oral and pharyngeal (oral) cancer, lip cancer, tongue cancer, oral cancer, salivary gland cancer, pharyngeal cancer, small intestine cancer, colon cancer, rectal cancer, kidney cancer, prostate cancer, vulvar cancer, thyroid cancer, colorectal cancer, endometrial cancer, uterine cancer, brain cancer, central nervous system cancer, peritoneal cancer, hepatocellular carcinoma, head cancer, neck cancer, Hodgkin disease and leukemia.